A transfer function method to predict building vibration and its application to railway defects

This work presents a simplified method to evaluate building shaking due to arbitrary base excitations, and an example application to railway problems. The model requires minimal computational effort and can be applied to a wide range of footing shapes, thus making it attractive for scoping-type analysis. It uses the soil excitation spectrum at the building footing location as it’s input, and computes the building response at any arbitrary location within it’s 3D structure. To show an application of the model versatility, it is used to compute building response due to a variety of singular railway defects (e.g. switches/crossings). It is however suitable for more general applications including railway problems without defects. The approach is novel because current railway scoping models do not use soil-structure transfer functions combined with free-field response to estimate building vibration by railway defects. First the soil-structure interaction approach is outlined for both rigid and flexible footings. Then it is validated by comparing results against a comprehensive fully-coupled 3D FEM-BEM model. Finally, it is used to analyse the effect of a variety of variables related to railway defects on building response. Local track defects are shown to have a strong influence on building vibrations. Further, vibration levels close to the threshold of human comfort are found in buildings close to the railway line. Overall the new approach allows for the computation of building vibrations accounting for soil-structure interaction, floor amplification and the measured/computed free-field response due to railway traffic using minimal computational effort

Numerical modelling of ground borne vibrations from high speed rail lines on embankments

A three dimensional numerical model is presented capable of modelling the propagation and transmission of ground vibration in the vicinity of high speed railways. It is used to investigate the effect of embankment constituent material on ground borne vibration levels at various distances from the track. The model is a time domain explicit, dynamic finite element model capable of simulating non-linear excitation mechanisms. The entire model, including the wheel/rail interface is fully coupled. To account for the unbounded nature of the soil structure an absorbing boundary condition (infinite element) is placed at the truncated interfaces. To increase boundary absorption performance, the soil structure is modelled using an elongated spherical geometry. The complex geometries associated with the track components are modelled in detail thus allowing a highly realistic simulation of force transmission from vehicle to embankment. Lastly, quasi-static and dynamic excitation mechanisms of the vehicle locomotives are described using a multi-body approach which is fully coupled to the track using non-linear Hertzian contact theory. The resulting model is verified using experimental ground borne vibration data from high speed trains, gathered through field trials. It is then used to investigate the role of embankments in the transmission of vibration. It is found that soft embankments exhibit large deflections and act as a waveguide for railway vibrations which are trapped within the structure. This results in increased vibration levels both inside the embankment and in the surrounding soil. In contrast it is found that embankments formed from stiffer material reduce vibrations in the near and far fields

Railway-induced ground vibrations – a review of vehicle effects

This paper is a review of the effect of vehicle characteristics on ground- and track borne-vibrations from railways. It combines traditional theory with modern thinking and uses a range of numerical analysis and experimental results to provide a broad analysis of the subject area. First, the effect of different train types on vibration propagation is investigated. Then, despite not being the focus of this work, numerical approaches to vibration propagation modelling within the track and soil are briefly touched upon. Next an in-depth discussion is presented related to the evolution of numerical models, with analysis of the suitability of various modelling approaches for analysing vehicle effects. The differences between quasi-static and dynamic characteristics are also discussed with insights into defects such as wheel/rail irregularities. Additionally, as an appendix, a modest database of train types are presented along with detailed information related to their physical attributes. It is hoped that this information may provide assistance to future researchers attempting to simulate railway vehicle vibrations. It is concluded that train type and the contact conditions at the wheel/rail interface can be influential in the generation of vibration. Therefore, where possible, when using numerical approach, the vehicle should be modelled in detail. Additionally, it was found that there are a wide variety of modelling approaches capable of simulating train types effects. If non-linear behaviour needs to be included in the model, then time domain simulations are preferable, however if the system can be assumed linear then frequency domain simulations are suitable due to their reduced computational demand

The Effect of Soil Non-linearity on Mixed Traffic Railway Lines: Passenger vs Freight Loads

To add additional capacity to railway networks, freight services might be added to lines that have previously only be used for passenger services. Existing ballasted lines may have mixed subgrade conditions and thus the effect of increased axle loads on track behavior is unclear. Typically, such cases will result in elevated track deflections in comparison to passenger vehicles. As a result, the supporting subgrade experiences higher strain levels, which can fall into the large strain range. The related non-linear subgrade behavior plays an important role in track response but is challenging to model. As a solution, this paper presents a new semi-analytical numerical model, where the track is simulated analytically and allows for 1D wave propagation. The ground is modelled using a non-linear equivalent thin-layer finite element formulation. This allows for the subgrade stiffness to be updated in an iterative manner with minimal computational effort. A case study is presented to show that modest increases in axle load can have a marked effect on track deflections

Salvage chemotherapy with high-dose leucovorin (LV) and 48-hour continuous infusion (CI) of 5-fluorouracil (5-FU) in combination with conventional doses of cyclophosphamide (CPM) in patients with metastatic breast cancer (MBC) pretreated with anthracycline and taxanes

The purpose of this study was to evaluate the activity and tolerance of high-dose leucovorin (LV) and infusional 5-fluorouracil (5-FU) in combination with conventional doses of cyclophosphamide (CPM) as salvage chemotherapy in patients with metastatic breast cancer (MBC) pretreated with anthracyclines and taxanes. 41 patients (median age 59 years) with MBC refractory or resistant to anthracyclines and taxanes were enrolled. The patients' performance status (WHO) was 0 in 10 patients (24%), 1 in 22 (54%), and 2 in 9 (22%). 30 (73%) patients had received 2 or more prior chemotherapy regimens. Cyclophosphamide (600 mg m−2) was given i.v. bolus on day 1 and LV (500 mg m−2 d−1) as a 2-h infusion followed by 5-FU (1.5 g m−2 d−1) over a 22 h c.i. for 2 consecutive days. Cyclophosphamide was administered every 28 days while 5-FU/LV every 14 days. In an intention-to-treat analysis, complete response (CR) was achieved in 2 (4.9%) patients and partial response (PR) in 9 (22%) (overall response rate 26.9%; 95% CI: 13.27–40.39%). Stable disease (SD) and progressive disease (PD) were observed in 9 (22%) and 21 (51%) patients, respectively. The overall response rate was 6% and 40% in patients with primary and secondary resistance to anthracyclines/taxanes, respectively (P = 0.047). The median duration of response and the median time to disease progression was 8 and 9.5 months, respectively. The median overall survival was 13 months and the probability for 1-year survival 51%. Grade 3/4 neutropenia occurred in 9 (22%) patients and 4 (9%) patients developed grade 3/4 thrombocytopenia. Non-haematological toxicity was mild. There were no cases of febrile neutropenia, toxic deaths or treatment-related hospital admissions due to toxicity. The combination of high-dose 5-FU/LV with conventional doses of cyclophosphamide is a well tolerated and effective salvage regimen in patients with MBC heavily pretreated with both anthracyclines and taxanes. © 2001 Cancer Research Campaignhttp://www.bjcancer.comhttp://www.bjcancer.co

Central nervous system relapse in patients with breast cancer is associated with advanced stages, with the presence of circulating occult tumor cells and with the HER2/neu status

INTRODUCTION: To evaluate the incidence of central nervous system (CNS) involvement in patients with breast cancer treated with a taxane-based chemotherapy regimen and to determine predictive factors for CNS relapse. METHODS: The medical files of patients with early breast cancer (n = 253) or advanced stage breast cancer (n = 239) as well of those with other solid tumors (n = 336) treated with or without a taxane-based chemotherapy regimen during a 42-month period were reviewed. HER2/neu overexpression was identified by immunohistochemistry, whereas cytokeratin 19 (CK-19) mRNA-positive circulating tumor cells (CTCs) in the peripheral blood were identified by real-time PCR. RESULTS: The incidence of CNS relapse was similar in patients suffering from breast cancer or other solid tumors (10.4% and 11.4%, respectively; P = 0.517). The incidence of CNS relapse was significantly higher in breast cancer patients with advanced disease (P = 0.041), visceral disease and bone disease (P = 0.036), in those who were treated with a taxane-containing regimen (P = 0.024), in those with HER2/neu-overexpressing tumors (P = 0.022) and, finally, in those with detectable CK-19 mRNA-positive CTCs (P = 0.008). Multivariate analysis revealed that the stage of disease (odds ratio, 0.23; 95% confidence interval, 0.007–0.23; P = 0.0001), the HER2/neu status (odds ratio, 29.4; 95% confidence interval, 7.51–101.21; P = 0.0001) and the presence of CK-19 mRNA-positive CTCs (odds ratio, 8.31; 95% confidence interval, 3.97–12.84; P = 0.001) were independent predictive factors for CNS relapse. CONCLUSION: CNS relapses are common among breast cancer patients treated with a taxane-based chemotherapy regimen, patients with HER2/neu-positive tumor and patients with CK-19 mRNA-positive CTCs

FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): a multicentre randomised phase III trial from the Hellenic Oncology Research Group (HORG)

To compare the efficacy and toxicity of oxaliplatin (L-OHP) in combination with irinotecan (CPT-11), 5-fluorouracil (5-FU) and leucovorin (LV) (FOLFOXIRI) vs irinotecan and 5-FU/LV (FOLFIRI) as first-line treatment of patients with metastatic colorectal cancer (MCC). A total of 283 chemotherapy-naïve patients with MCC were enrolled (FOLFIRI arm: n=146; FOLFOXIRI arm: n=137). In the FOLFOXIRI arm, CPT-11 (150 mg m−2) was given on d1, L-OHP (65 mg m−2) on d2, LV (200 mg m−2) on days 2 and 3 and 5-FU (400 mg m−2 as i.v. bolus and 600 mg m−2 as 22 h i.v. continuous infusion) on days 2 and 3. In the FOLFIRI arm, CPT-11 (180 mg m−2) was given on d1 whereas LV and 5-FU were administered in the same way as in the FOLFOXIRI regimen. Both regimens were administered every 2 weeks. There was no difference in terms of overall survival (median OS: 19.5 and 21.5 months, for FOLFIRI and FOLFOXIRI, respectively; P=0.337), median time to disease progression (FOLFIRI: 6.9 and FOLFOXIRI: 8.4 months; P=0.17), response rates (33.6 and 43% for FOLFIRI and FOLFOXIRI, respectively; P=0.168). Patients treated with FOLFOXIRI had a significantly higher incidence of alopecia (P=0.0001), diarrhoea (P=0.0001) and neurosensory toxicity (P=0.001) compared with patients treated with FOLFIRI. The present study failed to demonstrate any superiority of the FOLFOXIRI combination compared with the FOLFIRI regimen, although the observed median OS is one of the best ever reported in the literature

Selective Persulfide Detection Reveals Evolutionarily Conserved Antiaging Effects of S-Sulfhydration

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordData and Code Availability The raw data corresponding to the antibody microarray Detection of persulfidation of EGFR Pathway kinases represent entirely new application of the dimedone switch method and are therefore available in more detail from the corresponding author on request. Proteomic data used for Figure S2C are stored in Data S1 and S2 and for Figures S3H and S3I in Data S3 and S4. All in-gel persulfidation, as well as Western blot sufenylation and sulfynilation data are reported in main and supporting Figures. Other raw data are available at https://data.mendeley.com/datasets/pw2wz39tsk/2Life on Earth emerged in a hydrogen sulfide (H2S)-rich environment eons ago and with it protein persulfidation mediated by H2S evolved as a signaling mechanism. Protein persulfidation (S-sulfhydration) is a post-translational modification of reactive cysteine residues, which modulate protein structure and/or function. Persulfides are difficult to label and study due to their reactivity and similarity with cysteine. Here, we report a facile strategy for chemoselective persulfide bioconjugation using dimedone-based probes, to achieve highly selective, rapid, and robust persulfide labeling in biological samples with broad utility. Using this method, we show persulfidation is an evolutionarily conserved modification and waves of persulfidation are employed by cells to resolve sulfenylation and prevent irreversible cysteine overoxidation preserving protein function. We report an age-associated decline in persulfidation that is conserved across evolutionary boundaries. Accordingly, dietary or pharmacological interventions to increase persulfidation associate with increased longevity and improved capacity to cope with stress stimuli.IDEX BordeauxFRMMedical Research Council (MRC)Brian Ridge ScholarshipNorthcott Devon Medical Research FoundationMinistry of Education, Science and Technology Development of the Republic of SerbiaNIHDFG, GermanyAmerican Heart Association-Allen Initiative in Brain Health and Cognitive Impairmen